**13. The CARESS trial**

The SAPPHIRE trial (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) randomized patients with co-morbid conditions that represented exclusion criteria from the previous major randomized trials of CEA. The rationale was that patients with these co-morbid conditions appear to represent the majority of patients undergoing CEA, and concerns have been raised about the generalizability of the CEA trial results in view of the exclusion of those patients in major CEA trials. SAPPHIRE was designed to test "noninferiority" of CAS versus CEA in the high-risk population with >50% symptomatic or >80%

All carotid stenting procedures were done with the Angioguard protection device. The trial was conducted at 29 US centers which all had mean complication rate less than 3% for CEA and 4% for CAS. All patients were seen by a team made up of a neurologist, a surgeon, and an interventionist. If the surgeon felt that he or she could not operate, and the interventionist felt that intervention was possible, the patient was entered into a stent registry. Conversely, if the interventionist did not feel that he or she could perform the intervention, and the surgeon felt that surgery was possible, the patient was entered into a surgical registry. 723 patients were enrolled initially. Consensus was achieved in 307 patients who were randomized to either stenting (n = 156) or CEA (n = 151). The stent registry consisted of 409 patients, and the surgical registry included seven. Individual endpoints of death, stroke, and MI at 30 days were lower in patients randomized to stenting. The combined endpoint of death/stroke/MI was statisti‐ cally significantly lower in patients randomized to stenting vs. CEA. The death, stroke or myocardial infarction rate was 11.9% in the CAS group and 19.9 % in the CEA group after 1 year. The SAPPHIRE results indicated that CAS has become a promising alternative to CEA,

At 3 years, data were available for 260 patients (77.8%), including 85.6% of patients in the stenting group and 70.1% of those in the endarterectomy group. There was no significant difference could be shown in long-term outcomes between patients who underwent carotid artery stenting with an emboli-protection device and those who underwent endarterectomy The prespecified major secondary end point occurred in 41 patients in the stenting group (cumulative incidence, 24.6%; Kaplan–Meier estimate, 26.2%) and 45 patients in the endarter‐ ectomy group (cumulative incidence, 26.9%; Kaplan–Meier estimate, 30.3%) (absolute differ‐ ence in cumulative incidence for the stenting group, −2.3%; 95% confidence interval, −11.8 to 7.0). There were 15 strokes in each of the two groups, of which 11 in the stenting group and 9

The SAPPHIRE data are specific to patients who are at high surgical risk, and they provide no insight into outcomes of treatment of a carotid artery stenosis in patients at low-to-moderate risk. On the basis of the similar long-term outcomes among high-risk patients in the two treatment groups, it may be tempting to infer that endarterectomy is preferable for lower-risk

asymptomatic stenosis.[16, 17]

112 Carotid Artery Disease - From Bench to Bedside and Beyond

at least "not inferior".

patients.

**12. SAPPHIRE long-term results**

in the endarterectomy group were ipsilateral.[18]

Carotid REvascularization with Stenting Systems was a prospective, multicenter non-random‐ ized industry-sponsored trial compared standard CEA to carotid stenting in patients with symptomatic (≥50%) and asymptomatic (≥75%) carotid stenosis. There was no significant difference in the 30-day combined all-cause mortality and stroke rate between CEA (2%) and CAS (2%). There was no significant difference in the secondary endpoint of combined 30-day all-cause mortality, stroke, and myocardial infarction between CEA and CAS.[19]

Following the publication of the SAPPHIRE and the CARESS trials, carotid artery stenting rocketed. There was a general felling that carotid artery stenting will prevail and become the preferred choice for carotid revascularization. However, the following randomized trials did not come in favor of carotid stenting.
